There are more than 20,000 uncontrolled hazardous waste sites in the United States in urgent need of ranking and remediation. This research program is designed to develop a comprehensive biological/toxicological and chemical testing protocol which can be used to characterize and quantitate the potential toxicity of two major classes of chemical waste, namely oily (i.e. aromatic hydrocarbons, AHs) and wood-preserving wastes containing toxic halogenated aromatic hydrocarbon (HAH) contaminants. The HAHs include the polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), polychlorinated benzenes, polychlorinated phenols, polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), alkylated PCDFs, polychlorinated diphenylethers (PCDEs), and hydroxy-PCDEs. AHs and HAHs are invariably present in diverse analytes as highly complex mixtures of isomers and congeners and this complicates the hazard and risk assessment of these compounds. Research will focus on the development and validation of the toxic equivalency factor (TEF) approach for risk assessment of AHs and HAHs in which all compounds will be quantitatively ranked with respect to their potency relative to surrogate toxins such as benzo[a]pyrene and TCDD, respectively. The TEFs will be used to convert analytical data into toxic equivalents (TEs = TEF x concentration of the congener) and the bioassays will also be utilized for the direct determination of the TEs for mixtures or waste extracts. A series of (i) model compounds for structure- activity relationship (SAR) studies, (ii) congeners which are present in wood-preserving waste sites, (iii) reconstituted mixtures, and (iv) extracts from contaminated waste sites will be investigated in several in vivo and in vitro bioassays will be developed for quantitatively assessing the potential hazards/risks associated with the different classes of AHs and HAHs and their mixtures. These results will be correlated with analytical data to obtain an overall risk assessment of extracts from different sites. In addition, one project will focus on the potential human or environmental impacts at specific waste sites using human lymphocytes from workers or animals trapped on site. The overall program will also rely on an extensive preliminary risk assessment of twenty Superfund sites from which a minimum of seven sites will be selected for comprehensive site evaluation. The basis of site selection will include the nature of the toxic contaminants, accessibility, and the extent of proposed remediation. Ultimately, the risks associated with these sites before, during and after remediation will be estimated by chemical analysis and the battery of in vivo and in vitro bioassays which will be developed and validated by the different projects within this program. It is anticipated that this approach can be used in the future to assess the potential risks and hazards of other types of chemical waste.